Molecular mechanism underlying miR-130b-Sp1 transcriptional regulation in LPS-induced upregulation of MUC5AC in the bile duct epithelium

Hepatolithiasis is a common disease that represents a serious health threat to the Chinese population. The pathological mechanism underlying hepatolithiasis is closely related to bacterial infections of the intrahepatic bile duct, followed by chronic inflammation and the overexpression of mucin 5AC (MUC5AC). However, the exact mechanism responsible for the lipopolysaccharide (LPS)-induced upregulation of MUC5AC has yet to be elucidated. Specificity protein 1 (Sp1) is a ubiquitous transcription factor that plays a vital role in the regulation of a number of genes that are responsible for normal cellular function. microRNA (miR/miRNA)-130b is a member of the miRNA family. miRNAs can bind to the 3′-untralsated region (3′-UTR) of a target gene and influence its expression levels. The present study found that LPS increases the expression of MUC5AC by influencing Sp1 secretion. Chromatin immunoprecipitation-quantitative PCR experiments further verified three Sp1 binding sites in the MUC5AC promoter sequence that can regulate the expression of MUC5AC. Further analysis demonstrated that Sp1 expression was regulated by miR-130b. Luciferase experiments identified one miR-130b binding site in the Sp1 3′-UTR region. In vivo experiments also confirmed the role of the miR-130b-Sp1-MUC5AC signaling pathway in the formation of biliary stones and indicated that this pathway may provide targeted therapeutic strategies for the treatment of intrahepatic bile duct stones.